Aminoglycosides

                                    

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AMINOGLYCOSIDES

1. Examples
2. General properties
3. MOA
4. Shared toxicities
5. Gentamicin
6. Streptomycin
7. Amikacin
8. Gentamicin
9. Streptomycin
10. Amikacin
11. Sisomicin
12. Netilmycin
13. Neomycin
14. Kanamycin
15. Framycetin

 MOA

·        Bind with 30s ribosomal subunits

                          

                                      ↓    Inh. of protein synthesis

                                                             i.      Interfere with the initiation of P.S

                                                           ii.      Premature termination of translocation

                                                        iii.      Incorporation of incorrect AA

BACTERICIDAL

ž  Bind with 30s ribosomal subunits 

                              ↓       Inh. of protein synthesis

ž  Interfere with the initiation of P.S

ž  Premature termination of translocation

ž  Incorporation of incorrect AA

GENERAL PROPERTIES

1. Bactericidal,more at alkaline pH
2. Mainly on G-ve org
3. Not absorbed orally
4. Excreted unchanged in urine by GF

5. Protein synthesis inhibition
6. Used as sulfate salts
7. Narrow margin of safety
8. Common T :OT , NT & NMB
9. Only partial cross resistance

SHARED TOXICITIES

1. OTOTOXICITY :

ž  Dose & duration dependant

ž  Vestibular / cochlear

ž  Cochlear : hearing of high frequency → low frequency

ž  Elderly & pre–existing hearing defects

ž  Tinnitus first → progressive hearing loss.

        2. VESTIBULAR TOXICITY

ž  Headache first

ž  N , V, GIDDINESS, Nystagmus, vertigo, ataxia

ž  Poor recovery -elderly

        3. NEPHROTOXICITY

ž  Tubular damage

ž  Loss of urine conc. power

ž  Low GFR

ž  Nitrogen retention

ž  Albuminuria & casts

ž  Elderly & pre- existing renal disease

       4.  NMB :

ž  ↓ Ach release

ž  ↓ the sensitivity of the muscle end plates to Ach

STREPTOMYCIN

ž  Streptomyces griseus

    ANTIMICROBIAL  SPECTRUM

ž  Narrow

ž  Myco. tuberculosis. E.coli, proteins, shigella, pseudomonas, H.influenzae, H.ducreyi, Y.pestis, Brucella, Nocardia, Klebsiella

ADVERSE REACTION

1.    NT

2.    OT

3.    NMB

4.    Hs :rashes,eosinophilia, lymphadenopathy, dermatitis etc

5.    CNS : 8^th nerve damage

6.    Superinfection - rarely

     PREPARATION :

               Inj : 0.75,1gm powder /vial, I.M

      USES :

1.    TB

2.    Tularaemia

3.     Plaque

4.    m

5.    Sub acute bacterial endocarditis

GENTAMICIN

         Micromonospora purpurea

    ANTIMICROBIAL  SPECTRUM

        E.coli,proteus,Klebsiella, aerobacter, Salmonella, strepto, staph, pseudomonas

    USES

1. UTI
2. RTIs
3. Topically : burns, etc
4. Meningitis
5. SABE
6. Peritonitis
7. Prophylaxis

   PREPARATION

ž  Inj : 20mg /ml , 80mg/ ml vial

ž  Drops : 0.3%

ž  Oint : 0.1%

ž  Dose : 1-1.5 mg /kg /8^th hrly        I.M / I.V

AMIKACIN

ž  Broadest spectrum

ž  SS der. of kanamycin

ž  Resistant to 8 of 9 A. inactivating enzymes

  PREPARATION

ž  Inj : 100, 250, 500 mg in 2ml inj

ž  Dose : 1.5 mg /kg/day in 1-3 doses.

 

ANTIMICROBIAL  SPECTRUM

  E.coli, proteus, klebsiella, enterobacter, serratia, pseudomonas, myco.tuberculosis, certain atypical mycobacteria

SISOMICIN

ž  Micromonospora inyoensis

ž  More on pseudomonas

  PREPARATION

ž  50 mg , 10 mg/ml amp

ž  Oint.

FRAMYCETIN

ž  Streptomyces lavendula  ( decaris )

ž  Cream 1%, 0.5 %

ž  Eye drops : 0.5 %

NEOMYCIN

ž  Streptomyces fradiae

ž  G-ve & G+ve

ž  Highly toxic

ž  Not used systemically

ž  0.3 % oint, 0.5 % cream,

ž  350, 500mg tab

   USES

1. Topically: wounds, ulcers, burns etc
2. Orally :

            -Before bowel surgery

                   -Hepatic coma 

ADVERSE REACTION

1. Damage to int. villi –malabs with diarrhoea & steatorrhoea
2. ↓ vit K synthesis
3. ↓ Plasma cholesterol
4. Super infection with candida